The present invention relates to an improvement in measuring devices for blood clotting time.
Measurement of blood clotting time is widely employed to test blood coagulation functions. Typically known methods are Prothrombin Time measurement (PT) for testing the extrinsic coagulation system, Activated Partial Thromboplastine Time measurement (APTT) for the intrinsic system and Partial Thromboplastine Time measurement (PTT). There are also such methods as PT type coagulation time measurement (FAPT) and APTT type coagulation time measurement (FA-APTT) to study various factors of coagulation with the use of a sample which is diluted by a plasma devoid of coagulation factors. TT type coagulation time is also tested to learn the amount of fibrinogen present in the blood (FIBT).
The coagulation function of blood has heretofore been tested by measuring clotting time. Most of the reagents employed in the measurement of blood clotting time are made of organic extracts, and this may lead to an error that the same normal plasma may produce different results in measurement of clotting time when coagulation reagents of more than one production lot are used. Different results may be obtained even if the same normal plasma is measured for its clotting time when the reagents, made for identical purposes, were made of different materials or by different production methods.
The recent trend is that it is considered inappropriate to indicate the coagulation function in terms of clotting time. Instead, there has been an attempt to test the coagulation function by means of a ratio (R) or an activation value (A). In the former, the clotting time of normal plasma (Tn) is measured for every measurement to obtain a ratio value (R) by dividing the clotting time (T) of each sample by said normal plasma clotting time (Tn), that is R=T/Tn, which expresses coagulation function. The latter method employs an activation value, unit or concentration, since such values indicate the coagulation function more directly than the value R.
In the measurement of PT and APTT by the said latter (activation value) method, the normal plasma is first diluted with physiological saline solution (PSS). On the assumption that the plasma concentration of this diluted solution represents the activation value A (%) of the coagulation function, each diluted solution of different normal plasma concentration is measured for its clotting time. The normal plasma therefore has the activation value of 100%.
The relation of clotting time to activation value is plotted on graph, and a curve which coincides with each point of measured values is drawn. The curve is termed as the activation curve, which is used as a calibration curve to determine the activation value A from the clotting time T. It is therefore possible to determine the activation value A from the clotting time T, and it is possible to determine the activation value from the said curve in the graph if the clotting time of a patient's plasma is measured.
The coagulation function thus expressed in activation value from the activation curve instead of in clotting time shows an improvement in correspondency of its values with the coagulation function. Although its reproducibility was insufficient, it has been possible to obtain the activation curve of PT, whereas that of APTT was not obtainable. This is due to the fact that the detection of the clotting end point was not sufficient in the conventional clotting time measuring device. The method disclosed in U.S. Application Ser. No. 944,783, filed Sept. 22, 1978 (corresponding to Japanese Application No. 52-118730) enables the detection of the clotting end point, and the activation curve of APTT as well as that of PT can now be obtained with an excellent reproducibility.
FIG. 1 illustrates an activation curve of APTT which is obtained in accordance with the above method using the technique of U.S. Ser. No. 944,783. It is naturally preferable to measure the activation value A (%) directly by an on-line system. Now that activation curve is obtainable with a high reproducibility as mentioned above, it is possible to use an on-line system instead of conventional hand-plotted graphs.
However, the activation curve is not a mere linear or quadratic function, and therefore non-linear conversion of functions is required in order to indicate the activation value A from measured clotting time by an on-line system. The function which is easily assumed in a non-linear conversion such as this is an equation of higher degree. EQU y=a+bx+cx.sup.2 +dx.sup.3 +ex.sup.4 +fx.sup.5
However, it is not easy to determine the constants, a, b, c . . . in the above equation, and furthermore, these constants may vary depending on the production lots of the coagulation reagents.
The object of the present invention is to provide non-linear conversion from clotting time T to activation value Ac.